Nanobody-Based CD19/CD22 Tandem Dual CAR-T Therapy for R/R B-ALL

Korábbi kezelés

• History of autoimmune diseases requiring systemic immunosuppressive therapy within 2 years prior to signing the ICF, including but not limited to:
  • Crohn's disease
  • Rheumatoid arthritis
  • Systemic lupus erythematosus (SLE)
  • Systemic sclerosis
  • Inflammatory bowel disease (IBD)
  • Vasculitis
  • Psoriasis
• Presence of any uncontrolled active infection at the time of signing the ICF or within 4 weeks prior to apheresis that requires antibiotic, antiviral, or antifungal treatment.
• Receipt of any investigational drug therapy or other systemic antitumor therapy within 4 weeks before apheresis (or 5 half-lives of the drug, whichever is longer, as determined by the investigator).
• Receipt of extensive radiotherapy within 4 weeks prior to signing the ICF, except for palliative radiotherapy for non-target lesions within 2 weeks before signing the ICF or as expected during the study.
• Unresolved toxicity from prior antitumor therapy that has not returned to Grade 1 or baseline levels at the time of signing the ICF, except for hair loss and pigmentation (per NCI-CTCAE v5.0).
• Requirement for systemic corticosteroids or other immunosuppressive therapy (≥10 mg/day prednisone or equivalent) within 3 days prior to apheresis or during the study period, except for:
  • Intranasal, inhaled, or topical steroids, or localized steroid injections (e.g., intra-articular injections)
  • Systemic corticosteroids ≤10 mg/day prednisone (or equivalent physiological dose)
  • Steroids as prophylaxis for allergic reactions (e.g., pre-medication before contrast-enhanced CT)
  • Steroids used for symptomatic treatment of transfusion-related reactions
• Major surgery within 4 weeks prior to signing the ICF (excluding routine biopsy procedures) or planned major surgery during the study period.
• History of active tuberculosis infection within 1 year prior to signing the ICF, except for subjects with a history of tuberculosis more than 1 year ago, provided that the investigator determines there is no evidence of active tuberculosis.
• History of other primary malignancies within 5 years prior to signing the ICF, except for:
  • Adequately treated carcinoma in situ of the cervix
  • Localized basal cell carcinoma or squamous cell carcinoma of the skin
• Receipt of live-attenuated or inactivated vaccines within 4 weeks before signing the ICF or planned vaccination during the screening period.

Más betegség

• History of central nervous system (CNS) diseases, including but not limited to:
  • Epilepsy
  • Paralysis
  • Aphasia
  • Stroke
  • Severe brain injury
  • Dementia
  • Parkinson's disease
  • Neuropathy
• Positive virological or infectious disease markers, including:
  • Hepatitis B virus (HBV): Subjects with positive HBsAg or HBcAb-positive at screening must have undetectable HBV DNA in peripheral blood to be eligible; otherwise, they should be excluded.
  • Hepatitis C virus (HCV): Subjects with positive HCV antibodies and detectable HCV RNA should be excluded.
  • Human immunodeficiency virus (HIV) antibody-positive subjects should be excluded.
  • Cytomegalovirus (CMV) DNA test-positive subjects should be excluded.
  • Epstein-Barr virus (EBV) DNA test-positive subjects should be excluded.
  • Positive serological or non-specific antibodies for Treponema pallidum (syphilis).
• History of severe hypersensitivity or allergy to any components of the study drug.
• Any other condition or complication that, in the investigator's judgment, may affect adherence to the study protocol or make the subject unsuitable for participation.

Laborértékek

• Clinically significant cardiovascular diseases, including any of the following:
  • QTc interval ≥480 ms (Fridericia correction formula)
  • New York Heart Association (NYHA) Class II or higher heart failure
  • Unstable angina or acute myocardial infarction within 6 months prior to signing the ICF
  • Left ventricular ejection fraction (LVEF) <50%
  • Poorly controlled hypertension (as determined by the investigator)
  • Clinically significant arrhythmias or those requiring antiarrhythmic treatment, including:
  • Persistent ventricular tachycardia
  • Ventricular fibrillation
  • Torsades de pointes
  • Complete left bundle branch block

Egyéb

• Subjects who meet any of the following criteria will be excluded from the study:
• Pregnancy or lactation.

• The subject or their legally authorized representative (guardian) understands the study and voluntarily signs the informed consent form (ICF).
• Male or female, aged 12 to 65 years at the time of signing the ICF (inclusive of the cutoff values).
• Expected survival of at least 12 weeks. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at the time of signing the ICF.
• At the time of signing the ICF, the patient must be diagnosed with R/R B-ALL and meet the following criteria:
• Bone marrow morphological examination at screening shows >5% blasts in the bone marrow, and/or cerebrospinal fluid (CSF) analysis detects leukemic cells, and/or the presence of measurable extramedullary lesions, defined as:
  • Any lymph node or mass with an axial diameter >1.5 cm Any extranodal lesion with an axial diameter >1.0 cm
• Flow cytometry confirms CD19 or CD22 positivity in tumor cells from bone marrow, peripheral blood, or cerebrospinal fluid, or pathology confirms CD19 or CD22 positivity in lymph nodes/masses or extranodal lesions.
• Eligibility for Phase II (RP2D) is restricted to patients with R/R B-ALL who have failed prior immunotherapies, including blinatumomab, inotuzumab ozogamicin, or prior single-target CAR-T therapy.
  • Adequate organ function, meeting the following laboratory criteria:
• Liver function:
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5× upper limit of normal (ULN) Total bilirubin ≤2× ULN
• Renal function:
  • Adults: Serum creatinine clearance ≥60 mL/min (using the Cockcroft-Gault formula) or creatinine ≤1.5× ULN
  • Children: Serum creatinine levels must not exceed the following values:
  • 10-13 years: ≤1.2 mg/dL Males 13-16 years: ≤1.5 mg/dL Females ≥13 years: ≤1.4 mg/dL Males ≥16 years: ≤1.7 mg/dL Blood oxygen saturation (SpO₂) >92% on room air. Fertile male and female subjects of reproductive potential must agree to use effective contraception from the time of informed consent until 2 years after administration of the study drug.
  • Women of childbearing potential (WOCBP) include premenopausal women and those within 2 years post-menopause.
  • A negative blood pregnancy test is required for all female participants of childbearing potential at screening.